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145 Rituximab Maintenance after Autologous Stem Cell Transplantation Prolongs Survival in Younger Patients with Mantle Cell Lymphoma: Final Results of the Randomized Phase 3 LyMa Trial of the Lysa/Goelams GroupClinically Relevant Abstract

Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies
Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Therapeutic Approaches to Mantle Cell Lymphoma
Saturday, December 3, 2016: 12:00 PM
Ballroom 20CD (San Diego Convention Center)

Steven Le Gouill, MD, PhD1,2*, Catherine Thieblemont, MD, PhD3, Lucie Oberic, MD4*, Anne Moreau, MD5*, Krimo Bouabdallah, MD6*, Emmanuel Gyan, MD, PhD7, Gandhi Damaj8*, Vincent Ribrag, MD9, Pierre Feugier, MD, PhD10*, Olivier Casasnovas, MD11*, Hacene Zerazhi, MD12*, Corinne Haioun, MD, PhD13, Hervé Tilly, MD, PhD14, Olivier Tournilhac, MD, PhD15*, Herve Maisonneuve, MD16*, Philippe Solal-Celigny, MD17, Luc Mathieu Fornecker, MD, PhD18*, Eric W Van Den Neste, MD, PhD19, Danielle Canioni, MD20, Gilles Salles, MD, PhD21, Thierry Lamy, MD PhD22, Marie-Christine Bene, PharmD23*, Remy Gressin, MD24 and Olivier Hermine, MD, PhD25*

1Department of hematology, Nantes university Hospital and UMR892 INSERM, Nantes, France
2CHU de Nantes, INSERM UMR 892 équipe 10, Nantes, France
3Hôpital Saint-Louis, Paris, France
4Department of Hematology, Purpan University Hospital, Toulouse, France
5Department of Pathology, Nantes University Hospital, Nantes, France
6Haematology, CHU de Bordeaux, Bordeaux, France
7Service d'Hématologie et thérapie cellulaire, Centre Hospitalier Universitaire, Tours, France
8CHU d'Amiens, Amiens, France
9Gustave Roussy cancer campus, Villejuif, France
10CHU et INSERM 954, Nancy Université, Vandoeuvre Les Nancy, France
11Hematology Department, Hopital Le Bocage, CHU Dijon, Dijon, France
12hematology, CHG Avignon, Avignon, France
13Lymphoid Malignancies Unit, AP-HP, Groupe Hospitalier Mondor, Créteil, France
14INSERM U918, Centre Henri Becquerel, Rouen, France
15Service d'Hematologie Clinique et de Therapie Cellulaire, CHU, Universite d'Auvergne, EA7283, CIC501, Clermont-Ferrand, Clermont Ferrand, France
16Oncology and Hematology Department, CH, La Roche-sur-Yon, France
17Centre Jean Bernard, Le Mans, France
18Haematology, University Hospital, Strasbourg, France
19Department of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
20Pathology Department, Hopital Necker, Paris, France
21Hematologie, Hospices Civils de Lyon - Université de Lyon - UMR CNRS5239, Pierre-Benite, France
22INSERM U917, CHU Pontchaillou, Rennes, France
23Hopital Hotel Dieu, Laboratoire d'Hematologie, Nantes, France
24Hematology, CHU Grenoble, Grenoble, France
25Hematology Department, Necker University Hospital, AP-HP, Paris, France

Mantle cell lymphoma (MCL) accounts for approximately 6% of non-Hodgkin’s Lymphoma (NHL) in adults. MCL commonly responds to initial therapy but inevitably patients relapse and response duration decreases from one salvage therapy to the next. Indeed, there is an urgent need to control and/or eradicate residual MCL cells that are responsible for early and late relapses. Maintenance with Rituximab (RM) after R-CHOP has been shown to prolong OS in elderly MCL patients treated with R-CHOP (Kluin-Nelemans et al. NEJM). Induction with high-dose cytarabine followed by autologous stem cell transplant (ASCT) consolidation is standard of care for young patients but RM after ASCT has never been investigated so far. The LyMa trial (ClinicalTrials.gov, NCT00921414) is a prospective international randomized phase III trial that investigated RM after ASCT in young previously untreated MCL patients. Patients were included at diagnosis (<66y; stage >I, untreated, diagnosis of MCL according to WHO 2008 classification). Induction immuno-chemotherapy consisted of 4 courses of R-DHAP every 21 days (Rituximab, Dexamethasone, High-dose cytarabine, salt Platinum) followed by ASCT consolidation. Patients who were not in response (CR/CRu or PR) after R-DHAP received 4 additional courses of R-CHOP-14 before ASCT. The conditioning regimen for ASCT was R-BEAM. Patients in response after ASCT were randomized (1:1) between RM or no RM. RM consisted of one infusion of Rituximab (375mg/m2) every 2 months for 3 years. The primary endpoint was event-free survival (EFS) calculated from time of randomization; events were defined as disease progression, relapse, death, severe infection or allergy to Rituximab. Progression-free survival (PFS) and overall survival (OS) from time of diagnosis and time of randomization were secondary endpoints. The interim analysis showed a trend for a longer EFS and PFS in favor of RM arm. (Le Gouill et al, ASH 2014, abs 146). Herein, we present the results of the final analysis. RESULTS. Two hundred and ninety nine patients were enrolled from September 2008 to August 2012. Demographic and clinical characteristics of the patients were as followed: median age of 57y (27-65), 79% of male, MIPI-low in 53.2%, MIPI-I in 27.4% and MIPI-H in 19.4%. After inclusion, 277 patients completed the 4 courses of R-DHAP. The CR/CRu rate after R-DHAP was 77.3% and ORR was 89.3%. Twenty patients received R-CHOP. In all, 257 patients (including 12 patients who received R-DHAP/R-CHOP) underwent ASCT. After ASCT, 240 patients were randomized (RM, n=120; no RM, n=120). Median follow-up (mFU) from inclusion and from randomization were 54.4m (52.7-59.2) and 50.2m (46.5-54.2), respectively. The mPFS and mOS from inclusion in an intention to treat analysis were not reached; the 4y-PFS and OS were 67.8% (95%CI, 62.1 to 72.8) and 78% (95%CI; 72.8 to 82.3), respectively. According to EFS definition, 47 (39.2%) patients had an event in the no RM versus 25 (20.8%) in the RM arm. The mEFS from randomization was not reached in both arms. The 4y-EFS was 61.4% (95%CI; 51.3 to 69.9) in the no RM arm vs 78.9% (95%CI; 69.6 to 85.6) in the RM arm (p=0.0012). The EFS duration was significantly superior in the RM arm with a 54.3% reduction in the risk of event (Hazard ratio (HR)= 0.457; 95%CI, 0.28 to 0.74; p=0.0016). The median PFS and OS from randomization were not reached in both arms. The 4y-PFS and OS from randomization were superior in the RM arm: 82.2% (95%CI; 73.2 to 88.4) vs 64.6% (95%CI; 54.6 to 73) (p=0.0005) and 88.7% (95%CI; 80.7 to 93.5) vs 81.4% (95%CI; 72.3 to 87.7)(p=0.0413). Patients in the RM arm had a 60% reduction of risk of progression (HR=0.4; 95%CI, 0.23 to 0.68; p=0.0007) and a 50% reduction of risk of death (HR=0.5; 95%CI, 0.25 to 0.98; p=0.0454). The per protocol analysis yielded similar results.

In conclusion, The LyMa trial demonstrates for the first time that RM after ASCT prolongs EFS, PFS and OS. Thus, 4 courses of R-DHAP plus ASCT (without TBI) followed by RM maintenance (one infusion every 2 month for 3 years) is a new standard of care for young MCL patients.

Disclosures: Le Gouill: roche: Consultancy, Honoraria, Research Funding; janssen-cilag: Consultancy, Honoraria, Research Funding; celgene: Consultancy. Thieblemont: Gilead: Consultancy; Roche: Consultancy; Janssen: Consultancy. Ribrag: Pharmamar: Membership on an entity's Board of Directors or advisory committees; Esai: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; NanoString: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; ArgenX: Research Funding. Casasnovas: BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; ROCHE: Consultancy, Honoraria, Research Funding. Haioun: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hermine: Novartis: Research Funding; Celgene: Research Funding; Alexion: Research Funding; AB science: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau.

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